REVIEW: Protein Folding, Misfolding, and Aggregation. Formation of Inclusion Bodies and Aggresomes

K. A. Markossian^* and B. I. Kurganov

Bach Institute of Biochemistry, Russian Academy of Sciences, Leninsky pr. 33, Moscow 119071, Russia; fax: (7-095) 954-2732; E-mail: markossian@inbi.ras.ru

^* To whom correspondence should be addressed.

Received December 26, 2003; Revision received January 27, 2004

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In this review the mechanisms of protein folding, misfolding, and aggregation as well as the mechanisms of cell defense against toxic protein aggregates are considered. Misfolded and aggregated proteins in cells are exposed to chaperone-mediated refolding and are degraded by proteasomes if refolding is impossible. Proteolysis-stable protein aggregates accumulate, forming inclusion bodies. In eucaryotic cells, protein aggregates form structures in the pericentrosomal area that have been termed “aggresomes”. Formation of aggresomes in cells is a general cellular response to the presence of misfolded proteins when the degrading capacity of the cells is exceeded. The role of aggresomes in disturbance of the proteasomal system operation and in cellular death, particularly in the so-called “protein conformational diseases”, is discussed.

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KEY WORDS: folding, misfolding, aggregation, inclusion bodies, aggresomes, chaperones, proteasomes, microtubules

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